Arteriosclerosis is a disease that is characterized by a thickening and hardening of regions of an arterial wall. A particular type of arteriosclerosis is atherosclerosis, which affects the large arteries and is often the basis for coronary artery disease, aortic aneurysm, arterial disease of the lower extremities, and cerebrovascular disease. Atherosclerosis is characterized by the formation of fibrous plaques that contain a large number of smooth muscle cells, macrophages, collagen, extracellular lipid, and necrotic cell debris. The accumulation of material in a fibrous plaque results in narrowing of the blood vessel lumen which, in turn, restricts arterial blood flow. When the fibrous plaques become sufficiently large to block blood flow completely, the organs that are supplied by the artery undergo ischemia and necrosis. The accumulation of fibrous plaques also weaken the artery, an event which frequently results in rupture of the intima, aneurysm and hemorrhage. Moreover, fragments of the fibrous plaque may detach and form arterial emboli that can precipitate an aortic aneurysm or arterial disease of the lower extremities.
To date, the most frequently used methods for treating atherosclerosis include surgical procedures, drug therapies, and combinations of the foregoing. In general, the drug therapies for treating atherosclerosis are designed to prevent or reduce the accumulation of plaque material. For example, drugs such as diuretics, anti-adrenergic agents, vasodilators, angiotensin-converting enzyme inhibitors, renin inhibitors, and calcium channel antagonists have been used to treat conditions such as hypertension, hyperlipidemia, and hypercholesterolemia, which contribute to the development of atherosclerosis. Surgical methods for treating atherosclerosis include coronary bypass surgery, atherectomy, laser procedures, ultrasonic procedures, and balloon angioplasty. Such methods involve significant risk (e.g., of infection, death) to the patient and, even if successful, fibrous plaque formation frequently occurs at the site of vascular anastomoses, causing reocclusion of the surgically-treated vessel.
In view of the foregoing, a need still exists for improved drug therapies to replace or supplement the existina methods for treating atherosclerosis and related conditions that are mediated by fibrous plaque formation. Preferably, such drug therapies would be designed to reduce or prevent plaque formation at its earliest stages.